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U-M researchers find family of 'on switches' that cause prostate cancer

ANN ARBOR, Mich. Researchers at the University of Michigan Comprehensive Cancer Center have discovered how genes turn on the switch that leads to prostate cancer.

The team discovered that pieces of two chromosomes can trade places with each other and cause two genes to fuse together. The fused genes then override the off switch that keeps cells from growing uncontrollably, causing prostate cancer to develop.

By testing these gene fusions in mice and in cell cultures, the researchers showed that the fusions are what cause prostate cancer to develop. But its not just one set of genes that fuse. The researchers found that any one of several in a family of genes can become scrambled and fuse. Results of the study appear in the Aug. 2 issue of Nature.

Each of these switches, or gene fusions, represent different molecular subtypes. This tells us theres not just one type of prostate cancer. Its a more complex disease and potentially needs to be treated differently in each patient, says lead study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, a new U-M center whose goal is to translate research into real world practice.

The gene fusion research is the centerpiece project of the new center. In the current study, researchers found one of several abnormal gene fusions in the prostate cancer tissue samples they tested. In 2005, the researchers identified a prostate-specific gene called TMPRSS2, which fuses with either ERG or ETV1, two genes known to be involved in several types of cancer.

The Nature paper reports on five additional genes that fuse with ERG or ETV1 to cause prostate cancer. Gene fusions were involved in 60 percent to 70 percent of the prostate cancer cell lines the researchers looked at. The genes involved are all controlled by a different mechanism. For example, four of the genes are regulated by androgen, a male sex hormone known to fuel prostate cancer.
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Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
1-Aug-2007


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